Immunomodulatory properties and toxicity of interleukin 2 in patients with cancer.
We performed a phase Ia/Ib study of interleukin 2 (IL2) in patients with cancer. Single doses of IL2 from 10(3) units/m2 to 10(7) units/m2 were well tolerated but failed to induce significant immunological changes. Chronic IL2 treatment for 5 days out of 7 for 3 weeks was well tolerated at doses below 10(7) units/m2 and was accompanied by significant immunological changes. Following chronic treatment with intramuscular injections of IL2 at 1 x 10(6) units/m2, we observed augmentation of peripheral blood natural killer activity and induction of peripheral blood LAK activity. Induction of LAK activity was most evident when IL2 was included in the cytotoxicity assay. There was a marked increase in the number of peripheral blood mononuclear cells bearing the Leu-19 marker in association with the observed increases in natural killer and LAK activity. A small percentage of Leu-19+ cells coexpressed CD3. There was heterogeneous expression of the low affinity Fc receptor (CD16). In vivo induced Leu-19+ cells could be divided into two populations, dim and bright, based on the intensity of fluorescent staining with antibodies to Leu-19. The majority of Leu-19 bright cells were CD16- while the majority of Leu-19 dim cells were CD16+. In addition, the intensity of CD16 staining was higher for Leu-19 dim cells than for Leu-19 bright cells. Increases in the amounts of CD38 and CD8 antigens were also observed. Significant increases in serum levels of the soluble IL2 receptor were observed during treatment. One partial remission was noted in a woman with non-Hodgkin's lymphoma.
Urba
W J
WJ
Program Resources, Inc., National Cancer Institute-Frederick Cancer Research Facility, Maryland 21701.
Steis
R G
RG
Longo
D L
DL
Kopp
W C
WC
Maluish
A E
AE
Marcon
L
L
Nelson
D L
DL
Stevenson
H C
HC
Clark
J W
JW
D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004341:Drug Evaluation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use
D007376:Interleukin-2; D011994:Recombinant Proteins